Hepatocellular carcinoma （HCC） is a common malignant tumor with a high mortality rate， an insidious onset， and complex pathological mechanisms. In the tumor microenvironment， tumor-promoting immune cells protect tumor cells from immune attacks， while dysfunction of anti-tumor immune cells causes the inhibition of immune response， thereby leading to the continuous deterioration of cancer. In recent years， traditional Chinese medicine has shown good efficacy in the treatment of HCC， and it can inhibit the proliferation and metastasis of cancer cells by regulating immune cells. By analyzing related articles in China and globally， this article summarizes how immune cells affect the progression of HCC through the immunosuppressive pathway and how traditional Chinese medicine exerts an anti-HCC effect by regulating immune cells， in order to provide theoretical basis and reference for optimizing the treatment of HCC.

Objective:To explore the role of serum cholinesterase (CHE) levels in the prognosis of patients with acute decompensated heart failure (ADHF).Methods:Total of 244 consecutive patients with ADHF who were admitted to the emergency department and were successfully discharged were prospectively enrolled from January 2018 to June 2020. Patients were divided into groups according to the first and third quartile of CHE level and the clinical data, laboratory tests and other nutritional indices were recorded after discharge, and then were followed up. The primary end points were the composites of cardiovascular death and hospitalization for worsening HF (composite end points). The secondary end points were all-cause mortality and cardiovascular death. Cox proportional risk analysis, time-dependent Cox regression model or stratified cox regression were used to identify the risk of primary and secondary endpoints. Clinical, biomarker and the compound models of clinical and biomarker were constructed. Kaplan-Meier method was used to plot the survival curves of different groups and compare their differences. Receiver Operating characteristics (ROC) curves were used to compare the area under the curve for CHE levels and other nutritional or prognostic indicators to identify composite end-point events.Results:During a follow-up period of 350(100,683) days, 158 patients reached the composite end points. In the multivariable Cox analysis, cholinesterase level was significantly associated with the composite end points after adjustment for major confounders. Cox proportional risk analysis or time-dependent Cox regression model showed that CHE level was significantly associated with the composite end points, all-cause mortality and cardiovascular mortality in both clinical, biomarker and composite models (all P< 0.05). A Kaplan–Meier analysis revealed that patients with low cholinesterase levels had significantly greater risk of reaching the composite end points than those with middle or high cholinesterase levels (78.1% vs 66.7% vs. 46.7%, P<0.001); Cholinesterase level showed the largest area under the receiver operating characteristic curve (AUROC) of 0.736 (95% CI, 0.664-0.888) for prediction of the composite end points among other nutritional indices. The AUROC of the Global Meta-Analysis Group Chronic Heart Failure (MAGGIC) Risk Score for prediction of the composite end points was increased from 0.704 to 0.762 ( P=0.038), when cholinesterase level was added. Conclusions:Cholinesterase may serve as a simple and effective prognostic marker for predicting adverse outcomes in ADHF patients.

Objective To evaluate the predictive value of functional liver imaging score(FLIS)based on preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI for post-hepatectomy liver failure(PHLF)in patients with hepatocellular carcinoma(HCC).Methods The data of HCC patients who underwent extensive hepatectomy and preoperative Gd-EOB-DTPA enhanced MRI were analyzed retrospectively.The FLIS was scored based on the three features including liver parenchyma enhancement,biliary excretion and portal vein signal enhancement in hepatobiliary phase images,and the consistency between different observers was evaluated.Logistic regression model and receiver operating characteristic(ROC)curve were used to analyze the ability of FLIS to predict the PHLF.Results PHLF occurred in 29 of 120 HCC patients(24.2%).The intraclass correlation coefficient(ICC)of FLIS evaluated by two observers was 0.944.Multivariate logistic regression analysis showed that FLIS was an independent predictor of PHLF of HCC patients[odds ratio(OR)0.520,95%confidence interval(CI)0.355-0.726;P<0.001].The area under the curve(AUC)of FLIS for predicting the PHLF was 0.709,the optimal diagnostic threshold was 4,and the corresponding sensitivity and specificity were 78.0%and 58.6%.Conclusion Preoperative FLIS can predict the PHLF of HCC patients,which may help to make more accurate treatment plans for HCC patients.

Objective:To evaluate the effects of different types of psychological interventions on the fear of cancer recurrence through a network Meta-analysis.Methods:Randomized controlled trials on the effects of different types of psychological interventions on the fear of cancer recurrence were retrieved from PubMed, PsycINFO, Web of Science, The Cochrane Library, Embase, EBSCO, China Biomedical Literature Database, CNKI, Wanfang Database and Vip Database. The retrieval period was from the establishment of the database to December, 31 2022. Two researchers conducted literature screening, extraction and quality evaluation, and used Stata14.0 software to conduct network Meta-analysis.Results:A total of 29 pieces of research involving 3 068 cancer patients and 11 psychological intervention measures. The results of network Meta-analysis showed that narrative therapy, PERMA(Positive, Engagement, Relationship, Meaning, Accomplishment) happiness theory model, acceptance and commitment therapy and cognitive behavior therapy had statistically significant differences in the intervention effect on the fear of cancer recurrence compared with conventional nursing ( SMD values were -1.93--0.83, all P<0.05); there was no significant difference among narrative therapy, PERMA happiness model, acceptance and commitment therapy and gratitude-expansion behavior theory (all P>0.05). The results of the cumulative probability map showed the best intervention was narrative therapy. Conclusions:The results of this study suggest that narrative therapy, acceptance and commitment therapy, and cognitive behavior therapy may be effective psychological intervention measures to improve the fear of cancer recurrence. However, more studies are still needed for further verification.

Objective To investigate the role and mechanism of silent information regulator 1(SIRT1)-NOD-like receptor protein 3(NLRP3)axis in the effect of remifentanil against ischemia-reperfusion injury(IRI)in rat livers.SD rats were randomly divided into sham operation group(sham group),IRI group,IRI+remifentanil pretreatment group(IRI+RPC group),IRI+SIRT1 inhibitor EX-527 group(IRI+EX-527 group)and IRI+RPC+EX-527 group,with 8 rats in each group.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),interleukin(IL)-1β and IL-18 of rats in each group were detected.The liver tissue pathology was observed.The apoptosis rate of hepatocytes in rats was detected.The expressions of SIRT1,NLRP3,cleaved cysteinyl aspartate specific proteinase-1(Cleaved Caspase-1)and Gasdermin D(GSDMD)proteins in rat liver tissue were detected.Results Compared with the sham group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI group were increased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+RPC group were decreased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were decreased,the relative expression of SIRT1 protein in liver tissue was increased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were decreased;the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+EX-527 group were increased,the ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI+RPC group,the liver tissue pathological score and hepatocyte apoptosis rate in the IRI+RPC+EX-527 group were increased,the levels of ALT,AST,LDH,IL-1β,and IL-18 were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Conclusions SIRT1 may participate in the regulation of remifentanil against rat liver IRI by inhibiting NLRP3 mediated cell pyroptosis.

OBJECTIVE To identify the chemical constituents of the modified Yupingfengsan formula. METHODS UPLC-Q- Exactive Orbitrap-MS technology was adopted. The separation was performed on Waters BEH C18 column with acetonitrile （A）-0.1% formic acid solution （B） as mobile phase for gradient elution. The heating electrospray ionization was used for positive and negative ion mode scanning. The scanning range was m/z 50-1 500， and the spray voltage was 2 kV （positive ion mode） and 1.5 kV （negative ion mode）. The information of chemical constituents of modified Yupingfengsan formula was collected through literature review to establish a database； the structure of the constituent was identified based on the above database， relevant literature， and chromatography and mass spectrometry information of reference standards. RESULTS & CONCLUSIONS Totally 114 chemical constituents were identified from modified Yupingfengsan formula， including 31 flavonoids， 39 phenylpropanoids， 5 saponins， 8 terpenoids， 3 chromones， 3 curcuminoids， etc. Based on the comparison of reference standards， 8 constituents were ultimately determined， including magnoflorine， calycosin， calycosin glycoside， cimifugin， 5-O-methylvisammioside， sec-O- glucosylhamaudol， luteolin and mangiferin. These constituents mainly involved glycosylation cleavage， retro Diels-Alder fragmentation， glycosylation loss， neutral molecule loss and other fragmentation pathways.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Objective:To evaluate the role of autophagy in hydrogen-rich solution-induced reduction of remifentanil-induced hyperalgesia in rats.Methods:Thirty-two clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, were divided into 4 groups ( n=8 each) by a random number table method: incisional pain group (group I), remifentanil+ incisional pain group (group RI), hydrogen-rich solution+ remifentanil+ incisional pain group (group HRI), and hydrogen-rich solution + autophagy inhibitor+ remifentanil+ incisional pain group (MHRI group). The tail vein was catheterized, the equal volume of normal saline was intravenously infused for 60 min while the incisional pain model was developed in group I, and remifentanil was intravenously infused at a rate of 1 μg·kg -1·min -1 for 60 min while the incisional pain model was developed in RI, HRI and MHRI groups, hydrogen-rich solution 10 ml/kg was intraperitoneally injected at 10 min before preparing the model in group HRI, and 3-MA 15 mg/kg was intraperitoneally injected at 1 h before preparing the model in MHRI group, and the other treatments were similar to those previously described in group HRI. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were determined at 24 h before and 2, 6, 24 and 48 h after the end of infusion. The rats were sacrificed under anesthesia after the behavioral testing, and the lumbar enlargement segment of the spinal cord was removed for determination of the expression of microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), Beclin-1 and P62 by Western blot. Results:Compared with the baseline at T 0, the MWT was significantly decreased and TWL was shortened at T 1-4 in the four groups ( P<0.05). Compared with group I, the MWT was significantly decreased and TWL was shortened at T 1-4, the expression of LC3 II and Beclin-1 was up-regulated, and the expression of P62 was down-regulated in group RI and group HRI ( P<0.05). Compared with group RI, the MWT was significantly increased and TWL was prolonged at T 1-4 in group HRI and group MHRI, the expression of LC3 II and Beclin-1 was significantly up-regulated, and the expression of P62 was down-regulated in group HRI, and the expression of LC3 II and Beclin-1 was significantly down-regulated, and the expression of P62 was up-regulated in group MHRI ( P<0.05). Compared with group HRI, the MWT was significantly decreased and TWL was shortened at T 1-4, the expression of LC3 II and Beclin-1 was down-regulated, and the expression of P62 was up-regulated in group MHRI ( P<0.05). Conclusions:The mechanism by which hydrogen-rich solution alleviates hyperalgesia may be related to enhancing the level of autophagy in the spinal cord of rats with incisional pain induced by remifentanil.

Objective:To evaluate the effect of trehalose on oxygen-glucose deprivation and restoration (OGD/R) injury in H9C2 cells and the role of solute carrier family 7 member 11- (SLC7A11)-glutathione peroxidase 4 (GPX4) signaling pathway.Methods:Well-grown H9C2 cells were divided into 4 groups ( n=24 each) by the random number table method: control group (group C), OGD/R group (group O), OGD/R+ trehalose group (group OT) and OGD/R+ trehalose+ erastin group (group OTE). The cells were normally cultured in group C. In O, OT and OTE groups, the DMEM medium was replaced with EBSS medium, the cells were exposed to 5% CO 2-95% N 2 in an incubator at 37 ℃ for 6 h, and then the medium was replaced with DMEM medium supplemented with 6% fetal bovine serum to restore oxygen and glucose supply for 24 h. In group OT, trehalose at a final concentration of 50 mmol/L was added during restoration of oxygen and glucose supply. In group OTE, the SLC7A11 inhibitor erastin at a final concentration of 10 μmol/L was added at 8 h before oxygen-glucose deprivation, and trehalose at a final concentration of 50 mmol/L was added during restoration of oxygen and glucose supply. The cell viability, lactic dehydrogenase (LDH) activity, contents of glutathione (GSH), malondialdehyde (MDA) and iron, and reactive oxygen species (ROS) levels were measured at 24 h of restoration of oxygen and glucose supply. The expression of SLC7A11, GPX4, long-chain fatty acyl coenzyme A synthetase 4 (ACSL4), and ferritin heavy chain 1 (FTH1) was detected by Western blot. The structure of the mitochondrial morphology was observed with a transmission electron microscope. Results:Compared with group C, the cell viability and GSH content were significantly decreased, the LDH activity, contents of MDA and iron, and ROS level were increased, the expression of SLC7A11, GPX4 and FTH1 was down-regulated, and the expression of ACSL4 was up-regulated in group O ( P<0.05). Compared with group O, the cell viability and GSH content were significantly increased, the LDH activity, contents of MDA and iron, and ROS level were decreased, the expression of SLC7A11, GPX4 and FTH1 was up-regulated, and the expression of ACSL4 was down-regulated in group OT ( P<0.05). Compared with group OT, the cell viability and GSH content were significantly decreased, the LDH activity, contents of MDA and iron, and ROS levels were increased, the expression of SLC7A11, GPX4 and FTH1 was down-regulated, and the expression of ACSL4 was up-regulated in group OTE ( P<0.05). Conclusions:Trehalose can inhibit ferroptosis by activating the SLC7A11-GPX4 signaling pathway, thereby attenuating OGD/R injury in H9C2 cells.

Objective To construct and validate a risk prediction model for poor inhalation in chronic obstructive pulmonary disease(COPD)patients receiving inhaler therapy,providing a decision support tool for personalized prevention of poor inhalation.Methods A cross-sectional study was conducted to collect data related to COPD patients receiving inhaler therapy,forming a dataset.The dataset was randomly divided into a training set and a test set in a ratio of 4∶1.Four different methods for missing value imputation,3 methods for variable feature selection,and 18 machine learning algorithms were employed to successfully construct 216 models on the training set.The monte carlo simulation method was used for resampling in the test set to validate the models,with the area under curve(AUC),accuracy,precision,recall,and F1 score used to evaluate model performance.The optimal model was selected to build the poor inhalation prediction platform.Results A study involving 308 patients with COPD found that 135(43.8%)were at risk of adverse inhalation.Using 33 predictor variables,216 risk prediction models were developed.Of these models,the ensemble learning algorithm yielded the highest average AUC of 0.844,with a standard deviation of 0.058[95%CI=(0.843,0.845)].The differences in predictive performance among the 216 models were statistically significant(P＜0.01).Under the ensemble learning algorithm,adherence to inhaler use(38.087 4%),inhaler satisfaction(25.680 1%),literacy(24.031 3%),number of inhalers(5.482 3%),age(4.204 5%)and number of acute exacerbations in the past year(2.184 7%)contributed most to the predictive model.The model exhibited superior performance,with an AUC of 0.869 3,an accuracy of 83.87%,a precision of 86.96%,a recall of 74.07%,and an F1 score of 0.8.Conclusion This study has developed a predictive model for poor inhalation risk in COPD inhaler therapy patients using machine learning algorithms,which exhibits strong predictive capabilities and holds potential clinical application value.